Method of equilibrating and calibrating a partial pressure gas sensor

ABSTRACT

A SENSOR OF THE PARTIAL PRESSURE OF CARBON DIOXIDE IN BLOOD, OTHER FLUID, OR GASEOUS MIXTURE COMPRISES A REFERENCE HALF-CELL AND A SENSING HALF-CELL IMMERSED IN A COMMON ELECTROLYTE COMPRISING CHLORIDE AND BICARBONATE IONS. THE SENSING HALF-CELL MAY BE PALLADIUM-PALLADIUM OXIDE (PD-PDO) OR IRIDIUM-IRIDIUM OXIDE (IR-IRO) AND THE REFERENCE HALF-CELL MAY BE PALLADIUM-PALLADIUM OXIDE HALF-CELL IS A WIRE COATED AT ITS DISTAL END WITH ITS OWN OXIDE. THE REFERENCE HALF-CELL MAY BE A SILVER TUBE WHICH IS COATED ON ITS TIP WITH SILVER HALIDE AND SLIPPED OVER AN INSULATED SECTION OF THE WIRE. THE DISTAL ENDS OF THE TUBE AND WIRE ARE DIPPED INTO ELECTROLYTE WHICH ADHERES AND THEN INTO POLYMER WHICH FORMS A CARBON DIXIDE PERMEABLE AND ION-IMPERMEABLE MEMBRANE OR BARRIER ON THE WHOLE ASEMBLY WHE THE POLYMER CURES. THE PROXIMAL ENDS OF THE SILVER TUBE AND WIRE ARE CONNECTED BY MEANS OF A COAXIAL CABLE TO A HIGH IMPEDANCE VOLTMETER WHICH IS CALIBRATED IN TERMS OF PARTIAL PRESSURE OF CARBON DIOXIDE IN MILLIMETERS OF MERCURY. MEANS ARE PROVIDED FOR STANDARDIZING THE SENSOR AND KEEPING IT EQUILIBRATED DURING STORAGE.

July 16, 1974 R. A. MACUR METHOD OF EQUILIBRATING AND CALIBRATNG APARTIAL PRESSURE GAS SENSOR i971 Original Filed Jan` 29, 2 Sheets-SheetFIGA July 16, 1974 R. A. MACUR 3,324l57 METHOD OF EQUILIBRATING ANDCALIBRATTNG A PARTIAL PRESSURE GAS SENSOR Original Filed Jan. 29, 1971 2Sheets-Sheet MILLIVOLTS United States Patent O'ice 3,824,157 PatentedJuly 16, 1974 3,824,157 METHOD F EQUILIBRATING AND CALIBRAT- ING APARTIAL PRESSURE GAS SENSOR Robert A. Macur, Milwaukee, Wis., assignorto General Electric Company Original application Jan. 29, 1971, Ser. No.110,957, now Patent No. 3,719,576. Divided and this application Sept.18, 1972, Ser. No. 290,020

Int. Cl. G01n 27/00 U.S. Cl. 204--1 T 8 Claims ABSTRACT 0F THEDISCLOSURE A sensor of the partial pressure of carbon dioxide in blood,other iluid, or gaseous mixture comprises a reference half-cell and asensing half-cell immersed in a common electrolyte comprising chlorideand bicarbonate ions. The sensing half-cell may be palladium-palladiumoxide (Pd-PdO) or iridium-iridium oxide (Ir-IrO) and the referencehalf-cell may be silver-silver halide. The sensing half-cell is a wirecoated at its distal end with its own oxide. The reference half-cell maybe a silver tube which is coated on its tip with silver halide andslipped over an insulated section of the wire. The distal ends of thetube and wire are dipped into electrolyte which adheres and then into apolymer which forms a carbon dioxide permeable and ion-impermeablemembrane or barrier on the whole assembly when the polymer cures. Theproximal ends of the silver tube and wire are connected by means of acoaxial cable to a high impedance voltmeter which is calibrated in termsof partial pressure of carbon dioxide in millimeters of mercury. Meansare provided for standardizing the sensor and keeping it equilibratedduring storage.

This is a division of application Ser. No. 110,957 tiled Jan. 29, 1971,now Pat. No. 3,719,576.

BACKGROUND OF THE INVENTION When a human subject is anesthetized the pH,oxygen and carbon dioxide levels of the blood must be held withinpredetermined limits. These parameters are ordinarily controlled byadjusting the concentrations of the individual gases comprising theinhaled mixture and by controlling the subjects ventilation depth andrespiration rate. Heretofore, the attending anesthesiologist wouldobserve certain clinical signs which are indicative of the subjectsrespiration and make adjustments as required. By the time the signs werepronounced enough to observe, however, any of these important parameterscould be near a critical limit; so that a considerable time would elapsebefore it would be restored to normalcy. Of course, more time elapsedbefore the anesthesiologist knew if he had overcompensated and had theparameters trending toward their opposite limits. These problems can bemet only partially by performing a blood-gas analysis with conventionallaboratory techniques on blood drawn from the patient since, even if theanalysis were accurate, the actual bloodgas condition would in allprobability have changed signicantly from the time of taking the sample.

It is medically useful to know the blood parameters mentioned. They areimportant and interrelated. The pH value, indicating the acidity andalkalinity levels of the blood, is very critical since the patient is ina serious condition if the parameter goes outside the pH range of 6.8 to7.8. In view of the importance of measuring pH, new pH sensors have beendeveloped and are described in copending applicants, Ser. No. 33,198iiled Apr. 30, 1970, and Ser. No. 81,314 led Oct. 16, 1970 both of whichare assigned to the assignee of this application.

Blood pH varies with the carbon dioxide level of the blood. When carbondioxide level rises, the blood becomes more acidic and pH declinesnumerically. When the carbon dioxide level falls, the blood becomes morealkaline and pH rises numerically. However, blood is highly buttered sothat a large change in carbon dioxide level must occur before there is aconsiderable change in pH. This means that there is a considerable lagbetween the occurrence of inadequate or excesive ventilation and amanifestation of the condition by a large change in pH. However,experiments show that the carbon dioxide level of the blood changesrapidly and substantially in correspondence with changes in ventilationso it is evident that a real time in vivo sensor for carbon dioxidewould be highly desirable.

SUMMARY 'OF THE INVENTION A primary object of this invention is toprovide a sensor for measuring the carbon dioxide tension in a gasmixture or in blood or other fluid either in vivo or in vitro.

lOther objects are to provide a carbon dioxide sensor which is easy tomanufacture, convenient to use, rugged, reliable, precise, accurate,highly sensitive, compatible with blood, and small enough to beintroduced into a small isolated sample or into a blood vessel or otherbody tissue with minimum trauma to the subject.

A further object is to provide a sensor which is so inexpensive,compared to known devices in the same class, that it can be disposed ofafter a single use.

Another object is to provide a unique system for storing a carbondioxide sensor prior to use such that it is maintained in asubstantially gas-equilibrated state and may be gas and temperatureequilibrated, tested and calibrated expeditiously before it is inertedin a subject.

In general terms, a preferred embodiment of the new sensor compriseseither a palladium-palladium oxide electrode Wire or an iridium-iridiumoxide wire which has a layer of its own oxide formed on at least a partof its length and preferably near its distal end. Hereinafter, theelectrode wire will be called a core for convenience and to signify thatit may have various configurations.

In the preferred embodiment the core is an iridium or a palladium wirewhich has an insulating coating over most of its unoxidized region. Asilver tube is slipped over this coating. The distal end of the tubeadjacent the oxide layer of the core has a silver halide layerpreferably silver chloride, formed on it and as such it acts as areference half-cell or electrode in conjunction with the sameelectrolyte in which the oxide coated wire is immersed.

The proximal end of the core is connected to the center conductor of acoaxial cable and the corresponding end of the silver tube is connectedto the braid of the cable. The opposite end of the cable plugs into ahigh impedance voltmeter Whose scale is calibrated in terms of partialpressure of CO2 in millimeters of mercury.

The electrolyte in which the tip or distal ends of the sensor electrodesare immersed is preferably a iilm forming type which adheres when thetip is dipped into an aqueous electrolyte solution during assembly. Theaqueous electrolyte iilm is isolated from the fluid undergoing CO2measurement by a thin carbon dioxide permeable membrane which is alsoapplied by dipping almost the whole length of the sensor assembly in apolymer solution from which the solvent volatilizes to form thewaterproof gas permeable but ion impermeable membrane. The electro lytefilm is thereby confined.

After assembly, the sensor is inserted in a disposable plastic tubewhich is filled with saline or a solution which has about the samecomposition as the electrolyte within the sensor. This has severalpurposes including preventing loss of uid by evaporation through thethin membrane of the sensor during. storage. The plastic tube is alsopermeable to CO2 in which case the solution which it contains is kept inconstant equilibrium with CO2 of known partial pressure in a gas mixturein which the sensor is stored. The solution within the plastic tube isthereby equilibrate-d with CO?l at a pressure approximating thatexpected in the blood. The whole sensor assembly is finally placed in asealed plastic container to maintain sterility. Immediately before thesenor is used it is removed from the plastic container and together withthe saline lled tube the senor is inserted in a heated socket which hasits temperature controlled at 37 C. or body temperature. When the tubeand sensor are temperature equililbrated, the measuring instrument isadjusted to read the calibration gas concentration and then the sensormay be inserted into the blood stream to give an accurate reading withinits response time constant. A small Wire is also sealed into the wall ofthe plastic tube and contacts the solution therein. The free end of thiswire can be touched on a special electrode of the readout voltmeterbefore the sensor is calibrated. If touching the wire on the meterterminal produces a meter reading, it constitutes an indication that thegas permeable, ion impermeable membrane is unsound and the sensor shouldnot be temperature equilibrated or used.

How the foregoing objects and other more specific objects of theinvention are achieved will appear from time to time throughout thecourse of the ensuing detailed description of an embodiment of theinvention taken in conjunction with the drawings.

DESCRIPTION OF THE DRAWINGS FIG. l is a plan view of the new carbondioxide sensor assembly as it appears when it is ready for attachment toa readout instrument and for insertion in a blood vessel or other vesselcontaining fluid or gas;

FIG. 2 is an enlarged fragmentary cross section of the distal tip of thesensor;

FIG. 3 shows the sensor in one stage of assembly so as to reveal certainfeatures of its construction;

FIG. 4 shows the sensor in a stage of assembly which later than thatdepicted in the previous figure;

PIG. 5 is' a longitudinal cross section of part of the sensor assembly;

FIG. 6 shows the completed sensor inserted in a fluid filled tube as inthe case when it is in storage or undergoing calibration immediatelyprior to use;

FIG. 7 is a graph of partial pressure of carbon dioxide vesus millivoltsoutput from the sensor;

FIG. 8 shows a chamber in which sensors of the type herein described maybe stored in a controlled atmosphere and kept in gas equilibration priorto calibration and use; and

FIG. 9 is a perspective view of the carbon dioxide level readoutinstrument with the sensor connected.

DESCRIPTION OF A PREFERRED EMBODIMENT FIG. 1 shows a carbon dioxidepartial pressure sensor comprising an elongated composite electrodewhich is generally designated by the numeral 10. The distal end or tip11 is the active end and is located in the blood stream during use if itis the real time monitoring of blood CO2 level in vivo that is ofinterest. Of course, the sensor may also be used to analyze for thepartial pressure of CO2 in a gaseous mixture or in a fluid other thanblood which contains carbon dioxide.

The proximinal end of the sensor extends into a plastic cannula adapter12 which has a knurled cap 13 and a cylindrical extension 14. Electricalconnections between the components of sensor 10 and a coaxial cable 15are made within adapter 12 and sealed as will be described in greaterdetail later. Coaxial cable 1S is surrounded by an insulating strainrelief tube 16 which may be of any suitable fiexible plastic. The cable15 is terminated in a coaxial connector 17 which is conventional andwhich permits connecting the sensor to a readout instrument which willbe discussed later.

The sensor 10 may be used to determine carbon dioxide level of a sampleof blood or other fluid which has been extracted from the body, but itis used most advantageously for monitoring CO2 level of the blooddirectly in the body. The sensor is introduced into the blood stream bypassing it through a cannula, not shown, which perforates the subjectstissue and the underlying wall of the blood vessel. The cannula is astandard type which is suitably socketed at its external end to receivethe cylindrical extension 14 of the plastic sensor adapter to therebymake a seal against loss of blood. The active tip or distil end 11 ofthe sensor extends into the blood stream beyond the tip of the cannulaand is always in contact with flowing blood.

The new sensor accurately and precisely measures the partial pressure ofcarbon dioxide in blood or other iluid over a wide range so it may beused to measure either venous or arterial blood carbon dioxide levels.

The construction of the sensor may be understood most readily byexamining the distal end 11 as in FIG. 2 where it is shown magnified. Itis seen to comprise a number of substantially concentric elements thecenter one of which is a metal core wire 18 which is coated with its ownoxide over part of its length extending back from the tip as indicatedby the stippled region 19. This core wire 18 may be selected from theclass of palladium and iridium. The core wire 18 may also comprise acoating of one of these metals or alloys thereof on some other basemetal. The electrode core may have configurations other than a wire; forinstance, it could be a tube or a fiat strip so core wire 18 will merelybe identified as core 18 hereinafter. For intravascular work it shouldhave a small diameter preferably in the range of .001 inch to .060 inchalthough increasing or decreasing its size does not affect itssensitivity to pH changes by which it indirectly determines carbondioxide pressure changes that occur in the electrolyte medium 20 whichsurrounds the electrode tip. Alloys of iridium or palladium containingas little as 5% of these elements with gold or platinum may also be usedalone or may be deposited on a substrate of another metal or non-metalto serve as electrode 18. A method for forming the oxide coating on core18 will be discussed later.

Core 18 can be seen in FIG. 2 to be immersed in an electrolyte filmwhich is marked with the numeral 20. This electrolyte film is preferablyaqueous and is comprised of .0l molar sodium bicarbonate and 1.0 molarsodium chloride in this example. Bicarbonate ions can be derived fromother compounds too. Chloride ions may be derived from any compound thatdoes not interfer with the acid-base reaction. The molarity of theelectrolyte is not critical but is a trade-off between sensitivity and areasonably short time constant. The electrolyte compounds in solutionmay be mixed with a hydrophilic surfactant to wet the sensor elementsand a thickening agent may be added to enhance adhesion when dipping butthis is not necessary in all cases.

'Encapsulating electrolyte 20 as well as the oxided region 19 of core 18is a carbon dioxide permeable membrane 21 which may be only a 'fewthousandths of an inch or less thick. The oxide coated core 18 by itselfconstitutes a half-cell whose potential varies in response to variationsin pH of any fluid surrounding it as is described in the presentinventors copending application for a pH electrode ycited earlierherein. In the present case, however, the electrolyte 20 is the fluidwhose pH is being sensed. The pH of this fiuid is altered by permeationof carbon dioxide lthrough the membrane 21 from the surrounding blood orother carbon dioxide containing gas mixture or liuid, in which thesensor is immersed. Since the carbon dioxide permeates the membrane 21and the partial pressure of this gas in the sample equilibrates in theelectrolyte, it follows thaft the voltage produced by the sensor isrelated to carbon dioxide pressure and can be interpreted in terms ofcarbon dioxide partial pressure.

As is well known, the voltage o'f the sensing half-cell such as the onejust described cannot be easily measured directly nor is its absolutevalue readily determinable for various reasons including the diminutionof the voltage to substantially zero due to polarization when currentflows through any instrument that is used to detect the lvoltage. It isltherefore necessary to measure relative voltage changes that areelfectted by pH changes corresponding with carbon dioxide changes ascompared with the voltage derived from a reference electrode that iscoupled with the sensing electrode through the isolating electrolyte 20.

The reference electrode in this example is of the silver- Isilverchloride ty'pe, although it could be any halide except fluoride. Thereference electrode in this illustrative embodiment is comprised of athin silver tube 22 which is slipped over the oxide coated core 18 andis electtrically isolated from it by a thin insulating tube 23. Theinsulating coating 23 does not, of course, extend over the whole lengthof the oxide coated region since this region must be in conductiverelation with the electrolyte 20. The distal end of silver ltube 22 hasa silver chloride layer deposited on its inside and outside prior to thetime that the tube is assembled with the central core. The length ofthis silver chloride layer is demarked between the lead lines referencesnumerals 26 and 25. By way of example, the silver tube may have a boreof 20 mils and may be chlorided over 250 mils of its length although thelength of chloriding can be varied.

lBecause silver tube 22 fits loosely over insulating tube 23 a thinconcentric gap 27 is created between ithe silver chlorided region 25-26and the outside of the insulating tube. This thin gap admits someelectrolyte 20 as shown to enlarge the ion conduction path lbetween thesilver chlorided region and the oxide coated region 19 of core Wire 18.

'How the conductive elements of the sensor are connected at theirproximal ends to coaxial cable 15 can be seen best in the subassemblydepicted in FIG. 3. INolte here that the insulation 30 of coaxial cable15 is stripped from the central wire 31 of this cable and the wire isconnected by soldering or other suitable means directly to the baresensor electrode core wire 18 `at the interface 32 of these two wires.In preparation for connecting, as just described, the outer insulatinglayer 33 of coaxial cable 15 is stripped and the metal braid 34 of thecable is rolled back as shown in FIG. 3.

The silver tube 22 and the underlying insulating tube 23 aresubstantially coextensive with the core 18. In other words, silver tube22 is insulated from sensor core 18 at the proximal end under discussionas well as at the distal end of the sensor. After the coaxial cablecenter wire 31 is soldered to sensor core 18, as described above, a tube35 consisting preferably of a heat shrinkable polymer, such as Teflon orpolyethylene is slipped over the sensor from its distal end andsubjected to heat to shrink it and provide an insulating layer as shown.It is evident from inspection of FIG. 3 that heat shrinkable tube 3Seffects an insulating bridge between core insulation 30 of the coaxialcable and the exterior of the silver tube 22. When tthe outer insulatinglayer 33 of coaxial cable 15 is removed, the underlying metallic braid34 is exposed and is rolled back on itself as illustrated in FIG. 3.After the coaxial cable central wire 31 and core 18 are soldered andinsulated as described above, the cable braid 34 is extended so as tomake electrical contact with the exterior of silver tube 22. The end ofthe braid is then elec trically connected by any suitable means to thesilver tu'be in the region marked 36 in FIG. 4. Thus, lthere are twoconductive paths leading away from the sensor, one o'f which is thesensor core 18 connected to the central wire 31 of the coaxial cable andthe other of which is the silver tube 22 connected to the metallic braid34 of the cable 15.

The distal end is then dipped in the film forming electrolyte 20 whichcoats the oxide coated tip 19 as well as the chlorided region on theoutside of silver tube 22. The dis- -tal end should be dipped inelectrolyte suiciently far t0 coat it with the electrolyte at least asfar as the terminal point 26 of the silver chloride coating 24 on tube22 and the concentric gap 27 between tube 26 and electrode core 18 mustbe filled with electrolyte 20.

With a quantity of immiscible aqueous electrolyte adhering to its distalend, the sensor is dipped into a membrane forming polymer which isdissolved in a volatile solvent. The sensor should be immersed in lthepolymer solution to such depth that it extends over the end 33 of theoutside insulating layer of the coaxial cable at the proximal end of thesensor. The solvent is then allowed |to evaporate from the polymercoating which dries and forms a relatively tough thin membrane. Althoughthe membrane 21 is present primarily for the purpose of conducting CO2from the sample fluid to the electrolyte 20 at the active tip of thesensor, it is: nevertheless desirable to deposit the membrane on thesensor as far back as the end 33 of the coaxial cable insulation becausethe membrane contributes to the electrical insulation of the assemblyand acts as a blood compatible surface. Any foreign electrolytes orother contaminants that enter Ithe sensor assembly might developspurious voltages which would be detrimental to stable and preciseoperation of a high irnpedance device such as this sensor. When thesensor is in the stage of assembly thus far described, the insulatingstrain relief sleeve 16 and the plastic cannula adapter 12 are slippedover the entire sensor from the distal end. rI'hen all free spaces arelllled with a sealant such as epoxy resin 37 and the sensor iscom-plete.

A preferred material having a high 'CO2 transfer coeicient out of whichto form ithe carbon dioxide permeable membrane 21 is asilicone-polycarbonate block copolymer `such as is described in U.S.Tat. No. 3,189,622 which is assigned to the assignee of thisapplication. This material may be dissolved in either chloroform,methylene chloride or ethylene chloride which are all Volatile. Thesensor is then dipped into the solution one or more times, depending onthe concentration of the.` solute, and allowed to lair dry after eachdip so that a Continous hole-free membrane will be formed. Other bloodcompatible CO2 permeable and ion impermeable polymeric materials may beused in place of the aforementioned material.

It will be evident that a sensor such as that described above will besubject to loss of moisture by evaporation from electrolyte 20 duringthe period between manufacture and use. For this and other reasons whichwill be explained later, the sensor is inserted in a casing which inthis case is a plastic tube 40, see FIG 6, which is lled with saline orother fluid 41 such as a solution of the same chemical components whichare found in the electrolyte 20 solution inside of the sensor tip. Thesolution in plastic tube 40 should preferably be isotonic with respectto the electrolyte in the sensor. The plastic tube 40 may be made ofpolypropylene or other material that is permeable to carbon dioxide. Thefluid 41 is retained in tube 40 during storage of the sensor by virtueof the proximal end of the tube making a tight slip it seal withcylindrical extension 14 of cannula adapter 12 as can be seen in FIG. 6.Before tube 40 is lled with fluid 41, a thin wire 42 is sealed into theend of the tube so that one end is in Contact with fluid 41 and theother end is exposed. The purpose of wire 42, as will be explained ingreater detail later, is to permit making an electrical integrity testof the sensor before it is temperature equilibrated and calibrated priorto use in a subject. There will also be a further discussion later ofhow fluid 41 is kept in the condition wherein it has carbon dioxidedissolved in it to produce. a predetermined partial pressure which aidsin Calibrating the sensor immediately prior to use. The partial pressureof carbon dioxide in fluid 41 is close to that which is expected to :beencountered in a subject whose blood CO2 partial pressure is beingmonitored. This facilitates calibration before use.

Other ways of sealing the tube 40 to the sensor could also be used inplace of plastic adapter extension 4. For instance, an O-ring could beslipped over the sensor at any point along its length so it could beaccepted by a tube of appropriate size. In any case the volume of fluid41 inside of tube 40 should `be minimized to speed up gas equilibration.

After tube 40 is in place on the sensor as depicted in FIG. 6, theentire sensor and its connecting cable 15 is deposited in a sealedpackage 53, see FIG. 8, made of polyethylene or other material that ispermeable to carbon dioxide. A gas mixture of known carbon dioxideconcentration and the balance being air may be permeated into theenvelope 53 by means of the permeating chamber shown in FIG. 8. Thispackage may then be subjected to gamma radiation to sterilize thecontents which are up to that time clean but not sterile.

A sensor which is packaged as described above and surrounded in a gasmixture of carbon dioxide and air at ambient pressure will maintain thecarbon dioxide in the tube 40 so that the sensor may lbe calibratedwhile inside the tube 40, thereby keeping the sensor in a gas pressurestable and sterile condition during calibration.

It is desirable that the electrolyte of the sensor be equilibrated atsubstantially the level of blood carbon dioxide to expedite calibration,so the packaged electrodes are kept by the using medical facility in acovered box which is marked with the reference numeral 43 in FIG. 8.This box has a gas inlet tube 44 and an outlet tube 45. A Calibratinggas flows into box 43 by way of connecting tube 44 from a gas tank 46which is equipped with a conventional regulator 47. A rubber tube 48conducts the gas from regulator 47 to inlet tube 44 of box 43. Gaspressure within box 43 may be maintained near atmopsheric pressure byterminating outlet tube 45 with a tube 49 whose lower tip is immersed ina few millimeters of water 50 which is in a container 51. This containeris equipped with a discharge tube 52. It will thus be evident that gaspressure within box 43 will be substantially equal to the atmosphericpressure which prevails at the time an electrode package is to bewithdrawn from the container and the sensor calibrated for use. Othermeans such as a pin hole inlet orifice may be used to control the flowof gas at near atmospheric pressure through box 43.

In accordance with Daltons law, the partial pressure of a gas in amixture of gases is proportional to its mole fraction. In this case, theCalibrating gas in tank 46 is chosen so that the mole fraction of carbondioxide is 0.06. At a given atmospheric pressure and temperature, carbondioxide will thus produce a constant known partial pressure. Thus, ifstandard atmospheric pressure is assumed to prevail where the sensor isto be calibrated, it is only necessary to substract the partial pressureof water vapor which is 47 millimeters of mercury at 37 C. bodytemperature. Assuming that atmospheric pressure is 760 millimeters ofmercury, the remainder will be 713 millimeters of pressure after the 47millimeters of mercury pressure due to water vapor are substracted. Thistotal pressure of 713 millimeters of mercury is equal to the sum of thepartial pressures of oxygen, nitrogen, carbon dioxide, and the raregases. Thus, it turns out that when one is Calibrating at a total gaspressure of 713 millimeters of mercury there is a corresponding partialpressure for CO2 of about 43 millimeters of mercury, which is about thecenter point of the CO2 range expected in the blood. Of course,calibration of the sensor must take place within a short time after thepackage 53 is removed from the gas ambient within box 43 or the gasdissolved in tluid 41 within plastic tube 40 will no longer beequilibrated with the standard gas.

It was mentioned earlier that the voltage produced when the sensor isdeposited in blood is displayed on a voltrneter such as the one marked54 in the instrument 55 which is shown in FIG. 9 and is calibrated interms of CO2 pressure. This instrument has a high input impedanceamplifier, not shown, which amplifies the voltage received from sensor10 and uses them to drive meter S4. Instrument 55 is also used forCalibrating the sensor 10. For that purpose the instrument is providedwith a number of sockets 65 in which the sensor may be inserted forcalibration. The interiors of sockets 56 are held at a temperature of 37C. which approximates human body temperature. With the coaxial cableconnector 17 plugged into an appropriate connector socket 57 ininstrument 55 and with the fluid filled plastic tube 40 in place onsensor 10, the tube and sensor are inserted jointly into one of thethermostatically controlled heating sockets 56. Since the partialpressure of carbon dioxide in uid 41 within tube 40 is equilibrated at43 millimeters of mercury, the balancing potentiometer knob 58 of theinstrument may be adjusted until the meter scale reads 43 whichcorresponds with the CO2 pressure expressed in mil limeters of mercury.Thus, calibration of the sensor is made each time at a fixed temperatureand at a known partial pressure of CO2 which is close to that which isexpected in the blood. The partial pressure of carbon dioxide in fluid41 does not change appreciably during the short calibration time or acorrection could be made easily if it did change. The gain of the sensormay be matched with the gain of the readout instrument amplifier, notshown, by means of a suitable gain select knob, not shown. Plastic tube40 is removed after calibration is complete and the sensor 10 isinserted through a cannula which has previously been inserted in theblood vessel and partial pressure of carbon dioxide of the blood may bethereafter read directly from meter 54.

Prior to going ahead with calibration procedure just described, andbefore fluid filled tube 40 is removed from sensor 10, the test wire 42which extends from the fluid filled tube is contacted on a terminal 59in the front of instrument 55. This terminal is connected to one of theinput terminals to the meter amplifier within the instrument through theagency of a circuit, not shown, which operates at a frequency of about1000 Hz. so as to not disturb the electrolyte balance in the sensor.Thus, if the meter deflects when the tip of wire 42 extending fromplastic tape 40 is contacted on terminal 59, such deflection indicatesthat the sensor should be discarded rather than calibrated. This avoidsthe possibility of inserting a defective sensor in a patient in whichcase another one would have to be substituted after it was discovered byobserving spurious readings or no reading on meter 54.

As manufactured, different sensors may show a different output voltageat a single calibration point. In other words, different sensors of thesame type may have a slightly different gain. Thus, when Calibratingbefore use as described above, the single calibration point, such aspoint 60 in the FIG. 7 graph of output voltage, may have a greater orlesser ordinate for different sensors but their gain-slope lines wouldremain parallel to the typical line 61 of the graph. To preclude anerroneous readout, each sensor is labeled with a letter representing areadout instrument gain adjustment that must be set to cause itscalibration point to coincide with a selected point such as point 60.The readout instrument gain adjustment knob is marked with gain settingscorresponding to the factory test gain settings which are indicated bythe lettered label on each individual sensor package so that gain can beset before calibration begins.

The slope of the readout graph may also differ a little between sensorsas suggested by the different slope of dashed line 62 as compared withline 61 in FIG. 7. Variances in slope are immaterial, however, becauseeven near the end points the difference in ordinates is small andreasonably close to the calibration point which is about in the centerof the range of CO2 levels encountered in blood. The clinical range ofCO2 partial pressure in blood is about 10 to 160 millimeters of mercury,but a smaller range is more common.

Particular information for preparing and processing some of thecomponents of the sensor will now be discussed in detail. Consider firstpreparation of the oxide coating 19 on the palladium or iridium centralcore wire 18 or electrode of the sensor. Several methods for preparingthis wire are described in the copending application of the presentinventor which was cited above. An illustrative method will,nevertheless, be set forth here. A commercially pure but otherwiseuntreated iridium or palladium wire is immersed in either an aqueoussolution of potassium hydroxide or sodium hydroxide. The hydroxideconcentration is not critical and may range from 1N to saturation. Afterwithdrawal from the solution, the wetted portion of the wire is heatedin an oven to approximately 800 C. in oxygen or an air ambient to forman iridate or a pallidate coating. The preferred heating time at 800 C.is from 5 to 30 minutes. A longer time is acceptable, but a shorter timesometimes results in a less stable electrode. The above process isrepeated until a blue-black coating is formed. The heat treatment may becarried on anywhere in the temperature range of 700 C. to 1100 C. foriridium and at about 750 C. for palladium although 800 C. is preferredfor both and produces the most uniform results. Palladium oxidevolatilizes when over 800 C. A wire treated in this manner is cooled andthen immersed in distilled water for about 24 hours whereupon theiridate or pallidate breaks down into either iridium or palladium oxideand sodium or potassium oxide. The latter oxides convert to sodiumhydroxide or potassium hydroxide, respectively, in water and aredissolved oif. The remaining coating is either iridium or palladiumoxide 19, depending upon the elemental nature of the wire, and anundetermined amount of water of hydration. The electrode 18 is thendried and is ready for being insulated over part of its length asdescribed above after which it can be incorporated in the sensorassembly.

A good material for the carbon dioxide permeable membrane 21 is anorgano-polysiloxane-polycarbonate block copolymer which is described inU.S. Pat. No. 3,189,622 and is assigned to the assignee of thisapplication. A membrane of this material has a high transfer coefficientfor carbon dioxide. As generally indicated above, a 35% weight/volumesolution of the copolymer is made using a volatile solvent such aseither chloroform, methylene chloride or ethylene chloride. After theelectrolyte hlm is deposited by dipping the sensor tip, the whole sensorassembly is dipped into this copolymer solution one or more times todeposit a layer approximately 0.5 mil t0 1.0 mil thick, after which itis allowed to dry. The material has good insulating qualities so it isdesirable to dip the sensor deeply enough to deposit a membrane layerall the way back onto the part of coaxial cable 15 which is covered bysleeve 16. Other carbon dioxide membranes can be substituted for thematerial discussed in the preceding paragraph such as styrene butadiene,Viton rubber and silicone rubbers deposited out of a volatile solvent.With a membrane of the above indicated thickness, the minimum partialpressure of carbon dioxide at which the sensor will operate is about 5millimeters of mercury. There must always be some pressure driving forceto permeate the membrane.

The silver-silver halide electrode may take various forms other than thechloride tipped silver tube 22. For example, a fine silver wire may behalide coated over part of its length and then spiraled aroundinsulating layer 23 which surrounds oxide coated central wire 18. Insuch case, the halide coated region, preferably silver chloride, must bespaced from the oxide coating 19 of the central wire and both coatingsmust be in contact with electrolyte 20. An insulating tube or otherwiseshaped reference electrode can also be made by depositing silver on itsentire surface or in a strip and chloriding the same.

Methods for forming silver chloride coatings are well known andavailable from the literature.

The palladium or iridium electrode may have configurations other than athin wire such as 18 on which there is an oxide coating 19. For example,it may be a tube, a at strip or a disc although this geometry may not beas advantageous as a wire for in vivo use of the sensor. Moreover, acore of material other than either palladium or iridium may be usedprovided an impervious layer of one of these elements is deposited onthe core and the layer is oxided as prescribed above. Rhodium andplatinum which are in the same group in the periodic chart cannot besubstituted for palladium or iridium or an inoperative sensor willresult.

The electrolyte 20 lm forming solution may be prepared by making a0.005N to 0.01N solution of sodium bicarbonate in a 0.15N to 1.0Nsolution of sodium chloride. This solution may be mixed with 1 gram ofanionic wetting agent. The lm forming solution may be anionic, cationic,or neutral.

This hlm forming agent has suitable adherence to the sensor tip when itis dipped in the solution prior to ap` plication of outside membrane 21.

The potential of the silver-silver chloride reference half-cell usedherein is about 240 millivolts with reference to a standard hydrogencell and remains constant since the concentration of the chloride ionsin the electrolyte 20 remains constant. As pH increases with decreasingCO2, the potential measured by the millivoltmeter instrument 55 declinesat a slope of about -59 mv. The potential actually measured is thedifference between that of the sensing electrode and the silver chlorideelectrode. In actual cases the slope is about 43 mv. change per unit logchange in CO2. The temperature coeicient has been measured to be about1.07 mv./ C. A temperature correction need not ordinarily be made whenthe sensor is in use because body temperature is reasonably stable butit is preferably provided for in the instrumentation.

The illustrative embodiment of the new carbon dioxide sensor describedabove and the method of calibrating and using it are directed primarilyto a sensor whose design is particularized for measuring carbon dioxidepartial pressure of blood and other body fluids in vivo. Those skilledin the art will appreciate, however, that the sensor and its Calibratingtechniques can be adapted to measuring pure carbon dioxide pressure andthe partial pressure thereof in various media. For example, the sensormay be used to measure carbon dioxide generation as an indicator offermentation activity in beer and wine making processes, or it may beused to monitor carbon dioxide gas concentrations in spacecraftrebreather systems, or as a pollution control device in connection withanalyzing ue and exhaust gases. The scope of the invention is to bedetermined only by interpretation of the claims which follow.

I claim:

1. A method of equilibrating and Calibrating a sensor that is adapted tomeasure the partial pressure of a specic gas in a sample of blood, otheruid or a gas mixture including the steps of (a) enclosing at least theactive part of the sensor in a casing means which is permeable to thespecific gas and contains a uid,

(b) maintaining said encased sensor in an equilibrating ambient whichincludes the specific gas at a known partial pressure approximating thatof the specific gas of the sample,

(c) withdrawing said encased sensor from said gaseous ambient andconnecting it promptly to a readout instrument so as to read the partialpressure of the specific gas in the fluid, and

(d) adjusting said readout instrument until it reads a partial pressurecorresponding with the known partial pressure of the specific gas in thegaseous ambient which also corresponds with the partial pressure of thegas in the iluid.

2. The method set forth in Claim 1 including the step of temperatureequilibrating said sensor by:

(a) establishing the temperature of said casing means, fluid and sensorat approximately the temperature of the sample before adjuesting thereadout instrument.

3. The method set forth in Claim 1 including the step of:

(a) keeping said encased senor in a specific gas permeable containermeans at least until the time the encased sensor is removed from saidequilibrating gas ambient.

4. The method set forth in Claim 1 wherein:

(a) said encased sensor is held in a chamber means with saidequilibrating gas mixture flowing through it at ambient atmosphericpressure prior to withdrawing the encased sensor.

5. The method set forth in Claim 1 including the step of:

(a) following the steps of withdrawing said sensor from said gaseousambient and connecting it to said readout instrument by contacting witha terminal of said instrument a conductor that extends from said uid tooutside of said casing means, whereby to determine the electricalintegrity of said sensor by the response of the instrument.

6. A method for temperature and pressure equilibration and calibrationof a sensor of the partial pressure of carbon dioxide in blood or otheruid sample including the steps of:

(a) enclosing at least the active part of said sensor in a casing meanswhich is permeable to carbon dioxide and contains an electrolyte fluid,

(b) having a container located near the place where the sensor will beused and storing the encased sensor in the container,

(c) flowing a gaseous mixture of known carbon dioxide content and theother constituents of air through said container at ambient atmosphericpressure until the partial pressure of carbon dioxide in the electrolyteuid is equilibrated with the partial pressure of carbon dioxide in themixture, and

(d) withdrawing said encased sensor and connecting it with a readoutinstrument and then adjusting and Calibrating the instrument until thesensor reads the known partial pressure of the carbon dioxide of theencased fluid.

7. The invention set forth in Claim 6 including the steps of:

(a) establishing the temperature of the casing means and the sensor atapproximately the temperature of the sample after the encased sensor isremoved from the gas mixture and before the instrument is calibrated.

8. The method set forth in Claim 6 wherein:

(a) the partial pressure of the carbon dioxide in said gaseous mixtureis at a pressure which approximates the partial pressure of carbondioxide in the sample.

References Cited UNITED STATES PATENTS 2,913,386 11/1959 Clark 204-195 P3,672,843 6/1972 Rosse et al 204-195 P X 3,714,015 1/1973 Niedrach204-195 P GERALD L. KAPLAN, Primary Examiner Us. c1. XR.

23-232 E; 73-1 R; 128-2 E; 324-33

